Biochemistry · Topic
Nuclear receptors !
Fat-soluble hormones (steroids, thyroid hormone, vitamin D, retinoic acid) enter the cell and activate receptors that switch genes on or off.
Updated 2026-11-01
Key facts
- They are ligand-activated transcription factors, with a DNA-binding domain of two zinc fingers and a hormone-binding domain.
- Type I (glucocorticoid, mineralocorticoid, androgen, oestrogen, progesterone): they wait in the cytoplasm bound to HSP90 and travel to the nucleus with the hormone.
- Type II (thyroid hormone, vitamin D, retinoic acid, PPAR): they already sit on DNA as heterodimers with RXR, and the hormone swaps corepressors for coactivators.
- Their effect takes hours because new RNA and protein must be made.
In detail
- In blood these hormones travel bound to proteins (cortisol-binding globulin, sex hormone-binding globulin, thyroxine-binding globulin, albumin); only the free fraction enters the cell.
- The hormone crosses the membrane and binds the ligand-binding domain; the receptor changes shape and exposes the AF-2 surface, where coactivators bind.
- The receptor binds hormone response elements in DNA, usually repeated six-base sequences.
- Coactivators acetylate histones and open chromatin; corepressors do the opposite.
- The glucocorticoid receptor also represses inflammation genes by sequestering factors such as NF-κB and AP-1: the basis of its anti-inflammatory effects.
- Also called
- Intracellular hormone receptors
Clinical notes
- Drugs acting here: dexamethasone and prednisone (glucocorticoid), spironolactone (mineralocorticoid), tamoxifen (oestrogen), fibrates (PPARα) and thiazolidinediones (PPARγ).
- Androgen insensitivity (faulty androgen receptor) gives a female phenotype with a 46,XY karyotype.
- Vitamin D receptor mutations cause vitamin D-dependent rickets type 2, with high calcitriol.
- Oestrogens raise thyroxine-binding globulin: total T4 rises while free T4 stays the same.
Related conditions
Related
- Cortisol
- Aldosterone
- Triiodothyronine (T3)
- Vitamin D (calcitriol)
- Vitamin A (retinol)
- Steroid hormone synthesis (overview)
- Hormone classes and mechanisms
- G protein-coupled receptors and cAMP
Test yourself
Think of the answer, then tap the question to see it.
Where is the glucocorticoid receptor before it binds the hormone?
In the cytoplasm, bound to heat-shock proteins (HSP90); with the hormone it is released and enters the nucleus.
With which receptor do the thyroid and vitamin D receptors form heterodimers?
With the retinoid X receptor (RXR).
Why do steroid effects take hours?
Because they act by changing gene transcription, and making new RNA and proteins takes time.
Which structural motif does a nuclear receptor's DNA-binding domain use?
Two zinc fingers, which recognise the hormone response element.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: NR3C1: Glucocorticoid receptor (human) (UniProt, 2026); THRB: Thyroid hormone receptor beta (human) (UniProt, 2026); 3GWS: Crystal Structure of T3-Bound Thyroid Hormone Receptor (RCSB Protein Data Bank, 2026); 1M2Z: Crystal structure of a dimer complex of the human glucocorticoid receptor ligand-binding domain bound to dexamethasone and a TIF2 coactivator motif (RCSB Protein Data Bank, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).
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Representative model, for educational purposes only.